Podcast
Questions and Answers
What is the role of tumor suppressor genes (TSGs) in cellular functions?
What is the role of tumor suppressor genes (TSGs) in cellular functions?
What happens during loss of heterozygosity in tumor suppressor genes?
What happens during loss of heterozygosity in tumor suppressor genes?
How do oncogenes differ from tumor suppressor genes?
How do oncogenes differ from tumor suppressor genes?
What is typically required for the activation of an oncogene?
What is typically required for the activation of an oncogene?
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What is the relationship between mutation rates and clonal selection in cancer?
What is the relationship between mutation rates and clonal selection in cancer?
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What is the primary reason that not all cells in a tumor share the same genotype?
What is the primary reason that not all cells in a tumor share the same genotype?
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What leads to the selection of variant progeny in tumor evolution?
What leads to the selection of variant progeny in tumor evolution?
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Which gene is primarily associated with retinoblastoma?
Which gene is primarily associated with retinoblastoma?
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Which process contributes to tumor progression after the initial mutation?
Which process contributes to tumor progression after the initial mutation?
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How do cancer-associated genes function differently from their normal roles?
How do cancer-associated genes function differently from their normal roles?
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What is the significance of mismatch repair genes in familial cancer syndromes?
What is the significance of mismatch repair genes in familial cancer syndromes?
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What signifies the acquisition of somatic mutations in cancer cells?
What signifies the acquisition of somatic mutations in cancer cells?
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Which of the following is NOT listed as a chemical carcinogen?
Which of the following is NOT listed as a chemical carcinogen?
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Which cancer-associated gene is commonly linked to Li-Fraumeni Syndrome?
Which cancer-associated gene is commonly linked to Li-Fraumeni Syndrome?
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In the context of oncogenesis, why is an initial mutation insufficient to create a clinical tumor?
In the context of oncogenesis, why is an initial mutation insufficient to create a clinical tumor?
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What is a consequence of genomic instability in cancer cells?
What is a consequence of genomic instability in cancer cells?
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What percentage of cancer deaths in the UK are attributed to smoking?
What percentage of cancer deaths in the UK are attributed to smoking?
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The APC gene is primarily associated with which type of familial cancer syndrome?
The APC gene is primarily associated with which type of familial cancer syndrome?
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Which of the following is NOT a characteristic of tumor-associated genetic behavior?
Which of the following is NOT a characteristic of tumor-associated genetic behavior?
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Which of the following agents is classified as an alkylating agent?
Which of the following agents is classified as an alkylating agent?
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Which gene is specifically associated with familial breast and ovarian cancer syndromes?
Which gene is specifically associated with familial breast and ovarian cancer syndromes?
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What is a common misconception about tobacco related to cancer?
What is a common misconception about tobacco related to cancer?
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Which chemical is considered a significant risk factor for lung cancer?
Which chemical is considered a significant risk factor for lung cancer?
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What is a defining characteristic of ‘classic’ oncogenes?
What is a defining characteristic of ‘classic’ oncogenes?
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How do tumor suppressor genes generally function?
How do tumor suppressor genes generally function?
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What is the genetic behavior of tumor suppressor genes in relation to familial defects?
What is the genetic behavior of tumor suppressor genes in relation to familial defects?
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Which of the following genes is considered a classic oncogene?
Which of the following genes is considered a classic oncogene?
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Mutant ras behaves differently from normal ras in what key way?
Mutant ras behaves differently from normal ras in what key way?
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What role do growth factors play in oncogenesis?
What role do growth factors play in oncogenesis?
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Which of the following statements about tumor suppressor genes is true?
Which of the following statements about tumor suppressor genes is true?
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The action sites of classic oncogenes include all except which of the following?
The action sites of classic oncogenes include all except which of the following?
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Which statement about the balance between proto-oncogenes and tumor suppressor genes is correct?
Which statement about the balance between proto-oncogenes and tumor suppressor genes is correct?
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What type of effect do mutations in classic oncogenes usually exhibit?
What type of effect do mutations in classic oncogenes usually exhibit?
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Study Notes
Introduction to Cancer
- Cancer is a leading cause of morbidity and mortality worldwide.
- Projected to rise to 29 million cases in 2040.
- Estimated 18 million new cases and 9.6 million deaths per year.
Learning Objectives
- Part 1: Basic cancer facts, risk factors, and prevention strategies.
- Part 2: Tumour classification, nomenclature, staging, oncogenesis, oncogenes, and tumour suppressor genes.
Cancer Facts
- Global incidence:
- Americas: 21%
- Europe: 23.4%
- Africa: 5.8%
- Asia: 48.4%
- Oceania: 1.4%
- 18.1 million new cancer cases globally in 2018.
Cancer Types
- Incidence (2018):
- Lung: 11.6% (2.094 million)
- Breast: 11.6% (2.089 million)
- Colorectal: 10.2% (1.8 million)
- Stomach: 5.7% (1 million)
- Prostate: 7.1% (1.3 million)
- Mortality (2018):
- Lung: 18.4%
- Colorectal: 9.2%
- Breast: 6.6%
- Stomach: 8.2%
- Liver: 8.2%
Causes of Carcinogenesis/Cancer
- Tobacco
- Alcohol
- Overweight
- Physical inactivity
- Diet
- Environment
- Medication
- Infection
- Sun & radiation
- Reproductive factors
- Family history
Heredity
- Genes associated with cancer syndromes:
- RB1 (retinoblastoma)
- APC (familial polyposis)
- HNPCC (Lynch syndrome)- Mismatch repair genes
- BRCA 1&2 (breast and ovarian cancer)
- p53 (Li-Fraumeni Syndrome)
Chemical Carcinogens
- Alcohol
- Asbestos
- Wood dust
- Rubber, plastics, dyes
- Tar/bitumen
- Aflatoxin
- Alkylating agents
- Tobacco
Smoking
- Smoking causes over a quarter of cancer deaths in the UK.
- Nearly one in five cancer cases are linked to smoking.
- 25-40% of smokers die in middle age.
- 9 in 10 lung cancers are linked to smoking.
- First observed in 1950.
Tobacco & Cancer Risks
- Chronic Diseases: Effects of selected tobacco
- Substances | Effects
- Tar | Carcinogenesis
- Polycyclic aromatic hydrocarbons | Carcinogenesis
- Nicotine | Ganglionic stimulation and depression; tumour promotion
- Phenol| Tumor promotion; mucosal irritation
- Benzopyrene | Carcinogenesis
- Carbon monoxide | Impaired oxygen transport and utilization
- Formaldehyde | Toxicity to cilia; mucosal irritation
- Oxides of nitrogen | Toxicity to cilia; mucosal irritation
- Nitrosamines | Carcinogenesis
Cytochrome P450 (CYP)-mediated effects of Polycyclic Aromatic Hydrocarbons (PAHs)
- Metabolism of PAHs by CYP1A1/2, CYP1B1 leads to carcinogenesis.
Smoking Rates
- Smoking rates have decreased among adults and children in the UK.
Alcohol and Cancer
- Damages cells
- Breaks down cancer-causing chemicals
- Weakens absorption of nutrients
- Increases oestrogen levels linked to breast cancer.
- Increases weight gain.
- Drinking less alcohol could prevent 12,800 UK cancer cases annually.
Infectious Diseases
- Infectious agents cause about 16.1% of new cancer cases annually.
- Sub-Saharan Africa has a much high burden.
- Four main responsible infectious agents are:
- Helicobacter pylori
- Human papillomavirus
- Hepatitis B and C viruses
- Other infections (Epstein Barr Virus, Human herpes virus 8)
Obesity and Cancer
- Highly caloric diet (rich in fat and refined carbohydrates).
- Low physical activity.
- Obesity can cause 13 types of cancer.
Lifestyle
- Age
- Diet
- Ethnicity
- Occupation
- Deprivation
Age and Cancer
- Advancing age is a significant risk factor.
- Median age of cancer diagnosis is 66 years.
- One-fourth of new cases are diagnosed in people aged 65-74.
Diet and Cancer
-
Haem:
- Nitrates & nitrites
- Heterocyclic amines (HCAs)
- Polycyclic amines (PCAs)
Cancer Prevention and Control
- Between 30-50% of cancers are preventable.
- Reducing these impacts:
- Smoking
- Alcohol
- Physical activity, lifestyle, dietary factors, being overweight and obesity
- Radiation exposure
- Environmental pollutants
- Occupational carcinogens
- Infections
- Primary Prevention: Reducing exposure to risk factors (public information, education, legislation, international cooperation).
- Secondary Prevention: Early detection (cervical screening, breast screening, colorectal screening).
Population Screening
- Detecting individuals at risk.
- Early detection for treatment.
- Characterisation, molecular staging and therapy control.
Screening for Cancer
- Early detection is key for successful treatment.
- Screening is done through medical tests on healthy individuals.
- Reliable screening tests available for certain cancers (cervix, breast, colon).
Cancer Definitions and Nomenclature
- Cancer arises from accumulation of genetic changes conferring a survival advantage to the neoplastic cells.
Genetic Changes
- Cell proliferation is affected.
- Apoptosis is affected
- Tissue invasiveness is affected.
- Production of growth and angiogenic factors is affected.
- Ability to escape immune surveillance is affected.
Neoplasia
- Cell proliferation escapes normal control, leading to immortality and inappropriate cell numbers at an anatomical site.
- Poor cell differentiation correlates with worse tumour behaviour.
- Benign neoplasms grow in a compact mass, whereas malignant neoplasms grow invasively.
Dysplasia
- A pre-malignant change in cells (usually epithelium).
- Disordered growth, morphologic changes in the cell nucleus.
- Key nuclear changes include crowded/overlapping nuclei, large/irregular nuclei, uneven chromatin distribution, and increased mitotic activity.
Classification of Tumours
- Benign: Enclosed in a fibrous capsule, take up space, concern if interferes with surrounding tissue/vessels
- Malignant: Not contained, metastasis, invades tissues.
Classification of Neoplsams
- Major Categories:
- Epithelial
- Connective tissue
- Lymphoid and hematopoietic tissue
- Germ cells
Cancer Types based on Biology
- Carcinomas (epithelial)
- Sarcomas (mesenchymal)
- Lymphomas (lymphoid)
- Leukaemias (blood-based)
- Often prefixed with the specific cell type – Adenocarcinoma: glands – Leiomyosarcoma: smooth muscle cells – liposarcoma: fat cells
Growth and Spread of Malignant Neoplasms
- Direct invasion: into adjacent structures.
- Lymphatic invasion: to regional lymph nodes.
- Blood vessel spread: usually to lungs or liver.
- Across serosal surfaces: pleura, pericardium, peritoneum.
Grading and Staging of Tumours
-
Grade: Cytological differentiation, mitotic rate, (grade I-IV (Broder)).
- Low, intermediate, high.
-
Stage: Size of primary tumour, invasion extent of spread, lymph nodes metastasis.
- TNM classification: Tumour, Node, Metastases.
- Stages I-IV, specific criteria for cancer type.
TNM Classification
- T - Tumour: Size or direct extent of primary tumour.
- N - Node: Degree of spread to regional lymph nodes. – NO: no tumour spread. – N1: to closest or limited nodes – N2: extensive spread to adjacent nodes – N3: spread to distant nodes
- M - Metastasis: Presence of distant metastasis. – M0: no distant metastasis. – M1: distant metastasis.
Other Parameters
- G (1-4): Grade of cancer cells (low/high).
- R (0/1/2): Completeness of operation (cancer free margins).
Examples of Tumour Stages
- Small, low-grade cancer, no metastasis.
- Large, high-grade cancer; spread to regional lymph nodes and other organs.
Genetic Basis of Cancer
- Accumulated genetic alterations confer survival advantage to neoplastic cells.
- Two processes: mutation, clonal selection.
Types of Mutations
- Deletions (ranging from 1bp to megabases).
- Insertions (include duplications).
- Single base substitutions (missense, nonsense, splice site).
- Frameshift mutations.
Loss-of-Function Mutations
- Inactivate (complete or partial) gene function.
- Often recessive phenotypes.
Gain-of-Function Mutations
- Change gene product function to abnormal.
- Usually dominant phenotypes.
Basic Concepts in Oncogenesis
- Monoclonality: Initially in a single cell, then expansion.
- Clonal Selection: Variation occurs over time giving rise to selection of more robust cancerous cell variants.
- Tumour progression: Initial mutations that destabilise the genome lead to further mutations. This produces subclones with progressively malignant phenotypes.
Cancer Associated Genes
- Proto-oncogenes: Normal role in cell growth.
- Tumour suppressor genes: Function to suppress cell growth.
Types of Genes Associated with Cancer
- Oncogenes: Promote growth/division (e.g., ras, myc, erb-B2).
- Tumour suppressor genes (TSGs): Normally inhibit division (e.g., p53, Rb, BRCA-1, BRCA-2).
"Classic" Oncogenes
- Mutation or overexpression leading to overactivity of gene.
- Frequently involves point mutations, and dominant effect.
- Example: mutated ras signals even without growth factor.
Sites of Action of "Classic" Oncogenes
- Growth factors
- Growth factor receptors
- Signal transduction proteins
- Nuclear regulatory proteins
- Cell cycle regulators
Tumour Suppressor Genes
- Genes that normally suppress cell replication.
- Opposite to effects of proto-oncogenes.
- Normal cell growth depends on balance between oncogenes and TSGs.
Tumour Suppressor Genes - Genetics
- TSGs have recessive genetics; familial defects can be dominant.
- Defects in one allele allows normal function, but a second mutation results in complete loss of function.
Multistep Mutations in Colon Cancer
- Series of mutations cause progression through adenoma, carcinoma stages.
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Description
Explore the fundamentals of cancer, including its global impact, types, and risk factors. This quiz will cover essential cancer facts, prevention strategies, and the mechanisms of carcinogenesis. Understand the significance of statistics and classifications related to cancer incidence and mortality.
